A potentially effective strategy in the treatment of HIV infections is the use of the combination of two or more antiviral agents or the combination of antiviral agents with biological response modifiers. At present, a particularly attractive combination would appear to be 3'-azido-2', 3'-dideoxythymidine (AZT) with interferon (IFN). In addition to their antiviral effects, both AZT and INF have immunodulatory effects and both have been demonstrated to be of benefit clinically in the treatment of HIV-related diseases. Furthermore, it has been demonstrated that the combination of INF and AZT is synergistic in inhibiting HIV replication in vitro. Before large-scale randomized testing of this therapy can be undertaken, several questions need to be addressed. These include: 1) Can INF AZT be administered safely to patients in doses that produce beneficial effects? and 2) Which INF, INF-alpha, INF-beta, or INF-gamma, is optimal as all three INF's have theoretical advantages in combination with AZT. We plan to treat patients with symptomatic HIV infections (HIV culture positive) but who have a good performance status, more than 100 CD4+ lymphocytes, and little evidence of bone marrow compromise with either AZT alone, INF-alpha-AZT, INF-beta- AZT, or INF-gamma-AZT. We will randomize patients to these four treatments in cohorts of patients receiving escalating doses of INF. AZT will be administered throughout the study at the currently recommended dose. We will compare the INF-AZT combinations with AZT alone in terms of 1) clinical toxicities, 2) the antiviral effects of (HIV cultures), 3) immunologic benefit (CD4+ lymphocytes and delayed-type hypersensitivity skin testing), and 4) clinical benefit (e.g. weight gain, absence of infection, resolution of symptoms, and response of secondary cancers). We will use the results to design further Phase I, II, and III studies of combination therapy in all patients with HIV infections.